HRPP Manual Section 8-6

Modifications to an Approved Research Study

Revised Common Rule (2018 Requirements)

“Establish and follow written procedures for: . . . (iii) Ensuring prompt reporting to the IRB of proposed changes in a research activity, and for ensuring that investigators will conduct the research activity in accordance with the terms of the IRB approval until any proposed changes have been reviewed and approved by the IRB, except when necessary to eliminate apparent immediate hazards to the subject.” 45 CFR 46.108(a)(3)(iii) (2018 Requirements)

“An IRB may use the expedited review procedure to review the following:

(i) Some or all of the research appearing on the list described in paragraph (a) of this section, unless the reviewer determines that the study involves more than minimal risk;

(ii) Minor changes in previously approved research during the period for which approval is authorized; or

(iii) Research for which limited IRB review is a condition of exemption under §46.104(d)(2)(iii), (d)(3)(i)(C), and (d)(7) and (8).” 45 CFR 46.110(b)(1)(2018 Requirements)

Pre-2018 Common Rule and U.S. Food and Drug Administration (FDA)

“Written procedures which the IRB will follow . . . (iii) for ensuring prompt reporting to the IRB of proposed changes in a research activity, and for ensuring that such changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject.” 45 CFR 46.103(b)(4) (Pre-2018 Requirements)

“Follow written procedures: . . . (3) for ensuring prompt reporting to the IRB of changes in research activity; and (4) for ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects.” 21 CFR 50.108(a)

“An IRB may use the expedited review procedure to review either or both of the following:

(1) some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk

(2) minor changes in previously approved research during the period (of one year or less) for which approval is authorized.” 45 CFR 46.110 (b)(Pre-2018 Requirements), 21 CFR 56.110(b).

Any proposed change or modification to an approved non-exempt research study that affects human subjects (with certain limited exceptions discussed below), must be reviewed and approved by the Institutional Review Board (IRB) prior to implementation of the change. To apply for approval of a modification, the investigator must complete a modification submission and include any new and/or revised documents. For review of modifications as part of an exempt determination that required limited IRB review, see Human Research Protection Program (HRPP) Manual 8-1 “Exemptions.”

For studies subject to the 2018 Requirements (Revised Common Rule), the proposed modification may be reviewed under the expedited review procedure:

  • When the modification involves research activities that appears on the expedited review category list, unless the reviewer determines that the study involves more than minimal risk, or

  • For minor changes in previously approved research during the period for which approval is authorized (see Minor vs. Non-Minor below).

For studies subject to the Pre-2018 Requirements and/or the FDA, the proposed modification may be reviewed under the expedited review procedure:

  • When the modification involves research activities that appear on the expedited review category list and is found by the reviewer(s) to involve no more than minimal risk, or

  • For minor changes in previously approved research during the period (of one year or less) for which approval is authorized (see Minor vs. Non-Minor below).

The proposed modifications must be approved by the IRB before the changes are implemented with limited exceptions (see Immediate Change to Eliminate Hazard below). Modification approvals do not change the approval or expiration date (if there is one) of the research study; the modification approval approves the modification to the research study and allows investigators to begin using the modified or new documents, procedures, etc. The principal investigator (PI) will receive notification of approval and availability to access the modification approval letter and IRB-approved consent form(s) (if applicable) through the MSU IRB online system. See HRPP Manual 3-1 “MSU Human Research Protection Program Plan” for a description of the MSU IRB online system.

Immediate Change to Eliminate Hazard

When an immediate change in a research protocol is necessary to eliminate a hazard to subjects, the proposed change need not be reviewed by the IRB prior to its implementation. In such situations, however, investigators must report the change in protocol to the IRB immediately thereafter. See the HRPP Manual 9-5 “Unapproved Change in Protocol” for policies and procedures.

Minor vs. Non-Minor Changes

Minor Changes

A minor change is one that does not materially increase risk, does not materially decrease benefit, and does not does substantially change the aims or design of the study. A minor change is one that does not introduce risks that exceed those ordinarily encountered by the subjects in daily life or in the performance of routine physical or psychological examinations or tests. Minor modifications cannot include addition of procedures that:

  • Involve more than minimal risk or

  • Do not meet the criteria for expedited categories (1) – (7) of research that could be reviewed using the expedited procedure.

Minor changes may be reviewed using the expedited procedure. See HRPP Manual 8-2 “Expedited Review Procedure” for more information.

Non-Minor Changes

A change that is not minor is one that materially increases risk, materially decreases benefit, or substantially changes the aims or design of the study. If the change introduces risks to subjects that exceed those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests, the change would not be considered a minor change. Except for minor changes, defined above, a change that does not meet the criteria for expedited categories (1) – (7) of research cannot be reviewed using the expedited procedure.

A change that is not minor must be reviewed at the convened IRB meeting unless the change qualifies for expedited review because it involves research activities that appear on the expedited review category list and for studies subject to the Pre-2018 or FDA requirements, are also minimal risk.

If the research study’s review level does not already require committee review and the change requested is considered a non-minor change that does not otherwise qualify for expedited review, the study’s review level will be changed to full review. See HRPP Manual 8 “Types of IRB Review” for policies and procedures related to change in review level and/or category.

Use of the Expedited Review Procedure

The IRB member reviewing the research study makes the determination on whether the change qualifies for use of the expedited review procedure. The IRB chair, other reviewers, or other experts may be consulted to determine if the modification qualifies for expedited review. If the modification is minor or otherwise qualifies for expedited review, the modification will be reviewed using the expedited review procedure. See HRPP Manual 8-2 “Expedited Review Procedure.” If the modification is non-minor, when it is not clear if the modification is minor, or the modification involves addition of research activities that do not qualify for expedited review, the modification will be brought to the convened IRB for review. See HRPP Manual 8-3 “Committee Review Procedure” for the process. If the convened IRB determines that the changes qualify for expedited review, the research study will be reviewed using the expedited review procedure unless the change was approved by the convened IRB. An approval letter may be issued once IRB reviewer(s) or the convened IRB approve the change.

For studies subject to the 2018 Requirements, when the modification involves research activities that appears on the expedited review category list, but the reviewer determines that the study involves more than minimal risk, the rationale for the determination will be documented by the IRB using a standard form.

Materials Required for Submission

The investigator is required to complete the modification submission using the MSU IRB online system. The online modification submission includes a description of the change and whether the change increases the risk.  The investigators are required to submit any new or modified documents with the modification submission. Modification submissions will not be processed if the new or modified document is missing.

Mechanism(s) for Submission

MSU IRB modification submissions must be submitted via the MSU IRB online system. The PI or PI proxy must confirm through the submission process that they will conduct the study in accordance with the responsibilities of researchers. See HRPP Manual 4-6 “Responsibilities of Researchers.” Only the PI or PI proxy may submit a modification submission.

Submission Processing

The IRB staff checks for completeness (e.g., all questions answered, any new or modified documents attached). Incomplete submissions will be returned.

Ancillary Review(s)

If the modification adds or impacts an area where an ancillary reviewer is typically assigned for initial review, the ancillary reviewer(s) is assigned to the study by the IRB coordinator. Depending on the ancillary review type and need, a response may be needed from the ancillary reviewer before an approval letter can be released. See HRPP Manual 8-5 “Initial Review” for more information.

How Review is Conducted

See the following HRPP Manual sections for review procedures: 8-2 “Expedited Review Procedure” or 8-3 “Committee Review Procedure.”

IRB Member Considerations

The IRB member(s) is required to review and approve protocols using the criteria at federal regulations 45 CFR 46 and, for FDA research studies, 21 CFR 50 and 56. If the human subject research is conducted, supported, or otherwise subject to regulation by a federal department or agency, there may be requirements in addition to 45 CFR 46 that are specific to the federal department or agency. See HRPP Manual 2-2 “Federal Guidelines and Regulations.” The criteria for IRB must be met to approve or recommend approval of the submission. The IRB member(s) should utilize Section 6, “IRB Evaluation Criteria” of the HRPP Manual.

When reviewing modifications to an approved research study, the criteria for IRB approval must be met to approve the requested modification. The IRB member(s) should determine how the change may affect the IRB approval criteria (e.g., change in recruitment may affect the selection of subjects criteria for approval). The IRB member(s) should utilize HRPP Manual 6, “IRB Evaluation Criteria” to review the proposed change (e.g., informed consent section for changes to the informed consent process) as needed.

The IRB member(s) should, in particular, consider the following:

  • The type of change (modification vs. addition)

  • Whether there is a change in level of risk

  • Whether the change alters the research study’s review level and/or category (See HRPP Manual 8, “Types of IRB Review” for policies and procedures related to change in review level and/or category)

  • Overall effect of change on research study

  • Whether change requires a modification to the consent process and/or form

  • Whether the change involves:

    • Vulnerable populations

    • Addition of sensitive questions

    • Privacy and/or confidentiality considerations

  • Effect of the change on subjects’ willingness to continue the study

  • Whether information should be provided to past or currently enrolled subjects:

    • Use of an information sheet vs. re-consent

    • If provided, the adequacy of information sheet or re-consent document

  • Whether there are any significant new findings that arise from the review process and that might relate to subjects’ willingness to continue participation are provided to subjects

Applicability of the Revised Common Rule (2018 Requirements)

See HRPP Manual Section 4-11 “Applicability of the Revised Common Rule (2018 Requirements)” for a description of whether the Revised Common Rule (2018 Requirements) or the Pre-2018 Common Rule Requirements apply.

Additional Considerations

Research studies may require verification from sources other than the investigator that no material changes have occurred since previous IRB review. See HRPP Manual 8-7 “Renewed Approval” for IRB considerations to determine when further verification is needed.

This policy and procedure supersedes those previously drafted.

Approved By: Vice President of Research and Graduate Studies, 4-21-2005. Revision 1 approved by VP Research & Graduate Studies on 4-5-2006. Revision 2 approved by VP Research & Graduate Studies on 3-9-2008. Revision 3 approved by VP Research & Graduate Studies on 5-6-2008. Revision 4 approved by VP Research & Graduate Studies on 9-3-2009. Revision 5 approved by VP Research & Graduate Studies on 7-22-2011. Revision 6 approved by VP Research & Graduate Studies on 12-11-2015. Revision 7 approved by Assistant VP Regulatory Affairs on 6-27-2018. Revision 8 approved by Senior VP for Research and Innovation on 1-18-2019. Revision 9 approved by Assistant VP Regulatory Affairs on 12-7-2021.

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